Collective stresses drive competition between monolayers of normal and Ras-transformed cells

Area of Science:

• Cell biology
• Biophysics
• Cancer research

Background:

• Cell competition is crucial for tissue homeostasis and development.
• Aberrant cell migration is a hallmark of cancer, contributing to invasion and metastasis.
• The Ras oncogene plays a significant role in cell growth, differentiation, and survival.

Purpose of the Study:

• To investigate the spatial competition between normal and Ras-oncogene-expressing cells.
• To understand the biophysical mechanisms governing cell sheet interactions and migration dynamics.
• To quantify the impact of Ras oncogene expression on cellular collective behavior and mechanical properties.

Main Methods:

• Utilizing two distinct cell lines differing solely in Ras oncogene expression.
• Employing antagonistic migration assays towards a shared substrate.
• Analyzing cell velocity and traction forces before and after cell-cell contact.
• Applying a hydrodynamic model for collectively migrating cohesive cell sheets.

Main Results:

• The interface between cell populations consistently moved towards the normal cell population after contact.
• Hydrodynamic modeling successfully interpreted velocity and traction force data.
• Relative material parameters were estimated, indicating differences between the cell lines.
• Transformed cells, exhibiting larger collective stresses, displaced the wild-type cells.

Conclusions:

• Ras oncogene expression enhances the competitive ability of cells for space.
• Increased collective stress in transformed cells is the driving force behind their displacement of normal cells.
• The study provides a biophysical framework for understanding oncogene-driven competitive interactions in cell populations.